P2RX7 (purinergic receptor P2X, ligand-gated ion channel, 7)

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P2RX7 (purinergic receptor P2X, ligand-gated ion channel, 7)

Identity

Other names MGC20089

P2X7

P2Z

HGNC P2RX7

Location 12q24.31

DNA/RNA

Description The P2RX7 gene is comprised of 13 coding exons.

Transcription The full length transcript is 3135 bp long and 10 alternative splicing isoforms have been identified.

Pseudogene Not known.

Protein

Description The protein has 595 residues amino acids and compromises a 69 kDa calculated molecular weight. However, N-glycosylation in the extracellular loop increases the size of the P2X7 receptor to about 75-85 KDa; the protein is composed successively (from the N- to the C-terminus) by:

25 amino acid intracellular N-terminus
21 amino acid first transmembrane domain
288 amino acid extracellular loop
21 amino acid second transmembrane domain
240 amino acid intracellular C-terminal region

Expression In a wide variety of tissues including heart, liver, pancreas, thymus, skeletal muscle and brain, although in brain the expression is mainly restricted to microglia. It also has relevant expression and function in immune cells (mainly in antigen presenting cells, such as monocytes, macrophages and dendritic cells).

Localisation Mainly is found in the plasma membrane, however it also can be found in intracellular membrane compartments while trafficking to the plasma membrane.

Function Acts as a ligand gated ion channel, sensing high concentration of extracellular ATP. Responsible for ATP-dependent activation and release of proinflammatory cytokines of the interleukin-1 family, mainly interleukin-1beta, interleukin-18 and interleukin-1alpha, playing a pivotal role in inflammatory responses. Prolonged stimulation of the P2X7 receptor can lead to plasma membrane bleb formation, opening of pannexin-1 dependent membrane pores and eventual cell death.

Homology With other P2X receptors, with the higher homology with P2RX4. Excluding the unique C-terminal domain, homology is 39-49% with other P2X receptors.

Mutations

Germinal The human P2X7 receptor gene is highly polymorphic and more then 260 SNP have been described, only four loss-of-function and one gain-of-function SNP have been described to date:

Loss of protein function:
946 G to A (Arg-307 to Gln)

1068 G to A (Ala-348 to Thr)

1513 A to C (Glu-496 to Ala)

1729 T to A (Ile-568 to Asp)

Gain of protein function:
489 C to T (His-155 to Tyr)

Somatic Not known in human.

Implicated in

Entity Extrapulmonary tuberculosis

Note The P2RX7 1513C allele has been strongly associated with extrapulmonary tuberculosis. The allele was associated with a reduced killing of Mycobacterium tuberculosis by macrophages.

Entity Chronic lymphoid leukemia (CLL)

Note The 1513C allele of P2RX7 has been associated with the clinical course of patients affected by chronic lymphocytic leukemia (CLL).
There is a possible role for the P2X7 receptor in the susceptibility to familial CLL or, alternately, the 1513C allele may be in linkage disequilibrium with a nearby susceptibility gene.

Entity Various cancers, including breast cancer, prostate cancer, papillary thyroid cancer and neuroblastoma.

Note P2X7 receptor is overexpressed in a variety of cancers (see above). A detailed understanding of the mechanistic contribution mediated by P2RX7 has yet to be established. However, there is substantial evidence that the P2X7 receptor may mediate cell survival and growth by increasing the efficiency of oxidative phosphorylation and total intracellular ATP stores. Finally it has been proposed that the P2X7 receptor may be a candidate marker of papillary thyroid cancer.

External links

	Nomenclature
HGNC	P2RX7 8537
Entrez_Gene	P2RX7 5027 purinergic receptor P2X, ligand-gated ion channel, 7
	Cards
Atlas	P2RX7ID41623ch12q24
GeneCards	P2RX7
Ensembl	P2RX7 [Search_View] ENSG00000089041 [Gene_View]
Genatlas	P2RX7
GeneLynx	P2RX7
eGenome	P2RX7
euGene	5027
	Genomic and cartography
GoldenPath	P2RX7 - 12q24.31 chr12:120055061-120108241 + 12q24 [Description] (hg18-Mar_2006)
Ensembl	P2RX7 - 12q24 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	P2RX7
	Gene and transcription
Genbank	AB209709 [ ENTREZ ]
Genbank	AK090866 [ ENTREZ ]
Genbank	AK225163 [ ENTREZ ]
Genbank	AK290405 [ ENTREZ ]
Genbank	AY847298 [ ENTREZ ]
RefSeq	NM_002562 [ SRS ] NM_002562 [ ENTREZ ]
RefSeq	AC_000055 [ SRS ] AC_000055 [ ENTREZ ]
RefSeq	AC_000144 [ SRS ] AC_000144 [ ENTREZ ]
RefSeq	NC_000012 [ SRS ] NC_000012 [ ENTREZ ]
RefSeq	NT_009775 [ SRS ] NT_009775 [ ENTREZ ]
RefSeq	NW_001838063 [ SRS ] NW_001838063 [ ENTREZ ]
RefSeq	NW_925395 [ SRS ] NW_925395 [ ENTREZ ]
AceView	P2RX7 AceView - NCBI
Unigene	Hs.507102 [ SRS ] Hs.507102 [ NCBI ] HS507102 [ spliceNest ]
Fast-db	14226 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q0IJ51 [ SRS] Q0IJ51 [ EXPASY ] Q0IJ51 [ INTERPRO ] Q0IJ51 [ UNIPROT ]
Prosite	PS01212 P2X_RECEPTOR [ SRS ] PS01212 P2X_RECEPTOR [ Expasy ]
Interpro	IPR003050 P2X7_purnocptor [ SRS ] IPR003050 P2X7_purnocptor [ EBI ]
Interpro	IPR001429 P2X_purnocptor [ SRS ] IPR001429 P2X_purnocptor [ EBI ]
CluSTr	Q0IJ51
Pfam	PF00864 P2X_receptor [ SRS ] PF00864 P2X_receptor [ Sanger ] pfam00864 [ NCBI-CDD ]
Blocks	Q0IJ51
HPRD	03977
	Protein Interaction databases
DIP	Q0IJ51
IntAct	Q0IJ51
	Polymorphism : SNP, mutations, diseases
OMIM	151400;602566 [ map ]
GENECLINICS	151400;602566
SNP	P2RX7 [dbSNP-NCBI]
SNP	NM_002562 [SNP-NCI]
SNP	P2RX7 [GeneSNPs - Utah] P2RX7] [HGBASE - SRS]
HAPMAP	P2RX7 [HAPMAP]
COSMIC	P2RX7 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	P2RX7
	General knowledge
Family Browser	P2RX7 [UCSC Family Browser]
SOURCE	NM_002562
SMD	Hs.507102
SAGE	Hs.507102
GO	lipopolysaccharide binding [Amigo] lipopolysaccharide binding
GO	purinergic nucleotide receptor activity [Amigo] purinergic nucleotide receptor activity
GO	regulation of sodium ion transport [Amigo] regulation of sodium ion transport
GO	receptor activity [Amigo] receptor activity
GO	ATP-gated cation channel activity [Amigo] ATP-gated cation channel activity
GO	receptor binding [Amigo] receptor binding
GO	ion channel activity [Amigo] ion channel activity
GO	ATP binding [Amigo] ATP binding
GO	cytoplasm [Amigo] cytoplasm
GO	plasma membrane [Amigo] plasma membrane
GO	integral to plasma membrane [Amigo] integral to plasma membrane
GO	ion transport [Amigo] ion transport
GO	cell surface receptor linked signal transduction [Amigo] cell surface receptor linked signal transduction
GO	positive regulation of calcium ion transport into cytosol [Amigo] positive regulation of calcium ion transport into cytosol
GO	membrane [Amigo] membrane
GO	integral to membrane [Amigo] integral to membrane
GO	sensory perception of pain [Amigo] sensory perception of pain
GO	positive regulation of bone mineralization [Amigo] positive regulation of bone mineralization
GO	bleb [Amigo] bleb
GO	bleb formation [Amigo] bleb formation
GO	response to ATP [Amigo] response to ATP
GO	protein homodimerization activity [Amigo] protein homodimerization activity
GO	regulation of apoptosis [Amigo] regulation of apoptosis
GO	negative regulation of MAPKKK cascade [Amigo] negative regulation of MAPKKK cascade
GO	negative regulation of bone resorption [Amigo] negative regulation of bone resorption
GO	positive regulation of cytolysis [Amigo] positive regulation of cytolysis
GO	pore complex biogenesis [Amigo] pore complex biogenesis
GO	protein heterodimerization activity [Amigo] protein heterodimerization activity
GO	positive regulation of interleukin-1 beta secretion [Amigo] positive regulation of interleukin-1 beta secretion
GO	positive regulation of cytoskeleton organization and biogenesis [Amigo] positive regulation of cytoskeleton organization and biogenesis
GO	regulation of killing of cells of another organism [Amigo] regulation of killing of cells of another organism
GO	membrane depolarization [Amigo] membrane depolarization
KEGG	Calcium signaling pathway
KEGG	Neuroactive ligand-receptor interaction
PubGene	P2RX7
TreeFam	P2RX7
CTD	5027 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	P2RX7 Related clones (RZPD - Berlin)
	PubMed
PubMed	89 Pubmed reference(s) in LocusLink

Bibliography

The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7).

Surprenant A, Rassendren F, Kawashima E, North RA, Buell G

Science (New York, N.Y.). 1996 ; 272 (5262) : 735-738.

PMID 8614837

The permeabilizing ATP receptor, P2X7. Cloning and expression of a human cDNA.

Rassendren F, Buell GN, Virginio C, Collo G, North RA, Surprenant A

The Journal of biological chemistry. 1997 ; 272 (9) : 5482-5486.

PMID 9038151

A Glu-496 to Ala polymorphism leads to loss of function of the human P2X7 receptor.

Gu BJ, Zhang W, Worthington RA, Sluyter R, Dao-Ung P, Petrou S, Barden JA, Wiley JS

The Journal of biological chemistry. 2001 ; 276 (14) : 11135-11142.

PMID 11150303

P2X7 receptor expression in evolutive and indolent forms of chronic B lymphocytic leukemia.

Adinolfi E, Melchiorri L, Falzoni S, Chiozzi P, Morelli A, Tieghi A, Cuneo A, Castoldi G, Di Virgilio F, Baricordi OR

Blood. 2002 ; 99 (2) : 706-708.

PMID 11781259

Molecular physiology of P2X receptors.

North RA

Physiological reviews. 2002 ; 82 (4) : 1013-1067.

PMID 12270951

An Ile-568 to Asn polymorphism prevents normal trafficking and function of the human P2X7 receptor.

Wiley JS, Dao-Ung LP, Li C, Shemon AN, Gu BJ, Smart ML, Fuller SJ, Barden JA, Petrou S, Sluyter R

The Journal of biological chemistry. 2003 ; 278 (19) : 17108-17113.

PMID 12586825

Association of the 1513C polymorphism in the P2X7 gene with familial forms of chronic lymphocytic leukaemia.

Dao-Ung LP, Fuller SJ, Sluyter R, SkarRatt KK, Thunberg U, Tobin G, Byth K, Ban M, Rosenquist R, Stewart GJ, Wiley JS

British journal of haematology. 2004 ; 125 (6) : 815-817.

PMID 15180873

An Arg307 to Gln polymorphism within the ATP-binding site causes loss of function of the human P2X7 receptor.

Gu BJ, Sluyter R, Skarratt KK, Shemon AN, Dao-Ung LP, Fuller SJ, Barden JA, Clarke AL, Petrou S, Wiley JS

The Journal of biological chemistry. 2004 ; 279 (30) : 31287-31295.

PMID 15123679

Differentiation between cancerous and normal hyperplastic lobules in breast lesions.

Slater M, Danieletto S, Pooley M, Cheng Teh L, Gidley-Baird A, Barden JA

Breast cancer research and treatment. 2004 ; 83 (1) : 1-10.

PMID 14997049

Differentiation between cancerous and normal hyperplastic lobules in breast lesions.

Slater M, Danieletto S, Pooley M, Cheng Teh L, Gidley-Baird A, Barden JA

Breast cancer research and treatment. 2004 ; 83 (1) : 1-10.

PMID 14997049

Basal activation of the P2X7 ATP receptor elevates mitochondrial calcium and potential, increases cellular ATP levels, and promotes serum-independent growth.

Adinolfi E, Callegari MG, Ferrari D, Bolognesi C, Minelli M, Wieckowski MR, Pinton P, Rizzuto R, Di Virgilio F

Molecular biology of the cell. 2005 ; 16 (7) : 3260-3272.

PMID 15901833

A His-155 to Tyr polymorphism confers gain-of-function to the human P2X7 receptor of human leukemic lymphocytes.

Cabrini G, Falzoni S, Forchap SL, Pellegatti P, Balboni A, Agostini P, Cuneo A, Castoldi G, Baricordi OR, Di Virgilio F

Journal of immunology (Baltimore, Md. : 1950). 2005 ; 175 (1) : 82-89.

PMID 15972634

Identification and characterization of splice variants of the human P2X7 ATP channel.

Cheewatrakoolpong B, Gilchrest H, Anthes JC, Greenfeder S

Biochemical and biophysical research communications. 2005 ; 332 (1) : 17-27.

PMID 15896293

A truncated P2X7 receptor variant (P2X7-j) endogenously expressed in cervical cancer cells antagonizes the full-length P2X7 receptor through hetero-oligomerization.

Feng YH, Li X, Wang L, Zhou L, Gorodeski GI

The Journal of biological chemistry. 2006 ; 281 (25) : 17228-17237.

PMID 16624800

The P2X7 receptor: a key player in IL-1 processing and release.

Ferrari D, Pizzirani C, Adinolfi E, Lemoli RM, Curti A, Idzko M, Panther E, Di Virgilio F

Journal of immunology (Baltimore, Md. : 1950). 2006 ; 176 (7) : 3877-3883.

PMID 16547218

Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor.

Pelegrin P, Surprenant A

The EMBO journal. 2006 ; 25 (21) : 5071-5082.

PMID 17036048

The P2X7 receptor sustains the growth of human neuroblastoma cells through a substance P-dependent mechanism.

Raffaghello L, Chiozzi P, Falzoni S, Di Virgilio F, Pistoia V

Cancer research. 2006 ; 66 (2) : 907-914.

PMID 16424024

A polymorphism in the P2X7 gene increases susceptibility to extrapulmonary tuberculosis.

Fernando SL, Saunders BM, Sluyter R, Skarratt KK, Goldberg H, Marks GB, Wiley JS, Britton WJ

American journal of respiratory and critical care medicine. 2007 ; 175 (4) : 360-366.

PMID 17095747

Increased P2X7 receptor expression and function in thyroid papillary cancer: a new potential marker of the disease?

Solini A, Cuccato S, Ferrari D, Santini E, Gulinelli S, Callegari MG, Dardano A, Faviana P, Madec S, Di Virgilio F, Monzani F

Endocrinology. 2008 ; 149 (1) : 389-396.

PMID 17947359

REVIEW articles automatic search in PubMed

Last year publications automatic search in PubMed

Search in all EBI NCBI

Contributor(s)

Written 01-2008 Pablo Pelegrin, Annmarie Surprenant

Faculty of Life Science, Michael Smith Building, University of Manchester, Manchester, M13 9PT, UK

Citation

This paper should be referenced as such :
Pelegrin P, Surprenant A . P2RX7 (purinergic receptor P2X, ligand-gated ion channel, 7). Atlas Genet Cytogenet Oncol Haematol. January 2008 .
URL : http://AtlasGeneticsOncology.org/Genes/P2RX7ID41623ch12q24.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Mon Aug 11 21:16:09 2008

Home Genes Leukemias Solid Tumours Cancer-Prone Deep Insight Case Reports Journals Portal Teaching

For comments and suggestions or contributions, please contact us
j.l.huret@chu-poitiers.fr.

Other names	MGC20089
	P2X7
	P2Z
HGNC	P2RX7
Location	12q24.31

Description	The P2RX7 gene is comprised of 13 coding exons.
Transcription	The full length transcript is 3135 bp long and 10 alternative splicing isoforms have been identified.
Pseudogene	Not known.

Description	The protein has 595 residues amino acids and compromises a 69 kDa calculated molecular weight. However, N-glycosylation in the extracellular loop increases the size of the P2X7 receptor to about 75-85 KDa; the protein is composed successively (from the N- to the C-terminus) by: 25 amino acid intracellular N-terminus 21 amino acid first transmembrane domain 288 amino acid extracellular loop 21 amino acid second transmembrane domain 240 amino acid intracellular C-terminal region
Expression	In a wide variety of tissues including heart, liver, pancreas, thymus, skeletal muscle and brain, although in brain the expression is mainly restricted to microglia. It also has relevant expression and function in immune cells (mainly in antigen presenting cells, such as monocytes, macrophages and dendritic cells).
Localisation	Mainly is found in the plasma membrane, however it also can be found in intracellular membrane compartments while trafficking to the plasma membrane.
Function	Acts as a ligand gated ion channel, sensing high concentration of extracellular ATP. Responsible for ATP-dependent activation and release of proinflammatory cytokines of the interleukin-1 family, mainly interleukin-1beta, interleukin-18 and interleukin-1alpha, playing a pivotal role in inflammatory responses. Prolonged stimulation of the P2X7 receptor can lead to plasma membrane bleb formation, opening of pannexin-1 dependent membrane pores and eventual cell death.
Homology	With other P2X receptors, with the higher homology with P2RX4. Excluding the unique C-terminal domain, homology is 39-49% with other P2X receptors.

Germinal	The human P2X7 receptor gene is highly polymorphic and more then 260 SNP have been described, only four loss-of-function and one gain-of-function SNP have been described to date: Loss of protein function: 946 G to A (Arg-307 to Gln) 1068 G to A (Ala-348 to Thr) 1513 A to C (Glu-496 to Ala) 1729 T to A (Ile-568 to Asp) Gain of protein function: 489 C to T (His-155 to Tyr)
Somatic	Not known in human.

Entity	Extrapulmonary tuberculosis
Note	The P2RX7 1513C allele has been strongly associated with extrapulmonary tuberculosis. The allele was associated with a reduced killing of Mycobacterium tuberculosis by macrophages.

Entity	Chronic lymphoid leukemia (CLL)
Note	The 1513C allele of P2RX7 has been associated with the clinical course of patients affected by chronic lymphocytic leukemia (CLL). There is a possible role for the P2X7 receptor in the susceptibility to familial CLL or, alternately, the 1513C allele may be in linkage disequilibrium with a nearby susceptibility gene.

Entity	Various cancers, including breast cancer, prostate cancer, papillary thyroid cancer and neuroblastoma.
Note	P2X7 receptor is overexpressed in a variety of cancers (see above). A detailed understanding of the mechanistic contribution mediated by P2RX7 has yet to be established. However, there is substantial evidence that the P2X7 receptor may mediate cell survival and growth by increasing the efficiency of oxidative phosphorylation and total intracellular ATP stores. Finally it has been proposed that the P2X7 receptor may be a candidate marker of papillary thyroid cancer.

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Written	01-2008	Pablo Pelegrin, Annmarie Surprenant
		Faculty of Life Science, Michael Smith Building, University of Manchester, Manchester, M13 9PT, UK